Acute Intermittent Porphyria Workup

Updated: Jan 13, 2023
  • Author: Thomas G DeLoughery, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Laboratory Studies

The fundamental step in diagnosing acute intermittent porphyria (AIP) is to demonstrate increased urinary porphobilinogen secretion. If a patient has no increased secretion of porphobilinogen, (ie, a level of 0-4 mg/L during acute symptoms), acute porphyria is eliminated as a cause of the neurovisceral symptoms. [15, 16]

A spot urine test for porphobilinogen can rapidly provide the diagnosis; these tests detect porphobilinogen at levels greater than 6 mg/L. A common error is to order a urine porphyrin screen. Porphobilinogen, a porphyrin precursor, usually is not included in a urine porphyrin screen; it must be ordered specially.

AIP patients have elevated porphobilinogen between attacks. However, in some patients with a remote (years ago) history of attacks, porphobilinogen can return to the reference range.

Elevation of urine porphyrins, especially coporphobilinogen, is observed. This is caused by spontaneous polymerization of porphobilinogen in the urine. Nonspecific (1-2 times reference range) elevation of urine porphyrins, especially coproporphyrins, is common and is not specific for porphyria. Stool porphyrins are within the reference range or mildly elevated.

Other nonspecific signs in an attack of AIP include the following:

  • Hyponatremia
  • Syndrome of inappropriate secretion of antidiuretic hormone (SIADH)
  • Mild leukocytosis

Although a defective enzyme causes AIP, measuring the activity of porphobilinogen deaminase is of little value. Approximately 10% of AIP patients will have normal activity because a different form of the enzyme is expressed in the hematopoietic tissues. The vast majority of patients with the defective enzyme do not have any symptoms of the disease.


Imaging Studies

Imaging studies are usually not helpful. Abdominal films will sometimes demonstrate an ileus. Findings on cranial computed tomography (CT) scan are normal.

Brain magnetic resonance imaging (MRI) scans occasionally show signs of increased edema in patients having very severe attacks. In patients with seizures, MRI may demonstrate parieto-occipital gyriform lesions on T2-weighted images that are characteristic of posterior reversible encephalopathy syndrome (PRES). [17]


Other Tests

Attacks of AIP are clinically indistinguishable from those of hereditary coproporphyria and variegate porphyria, and there are few evidence-based diagnostic strategies for these conditions. Whatley et al conducted a retrospective analysis of 467 unrelated patients to determine the diagnostic sensitivity of mutation analysis of the HMBS, CPOX, or PPOX gene. [18] Findings included the following [18] :

  • In the presence of increased porphobilinogen excretion, plasma fluorescence scanning and the coproporphyrin ratio can identify the type of acute porphyria, with rare exceptions.

  • In cases in which the porphobilinogen, 5-aminolevulinate, and porphyrin analyses are within reference intervals and in which there is high suspicion of a previous illness caused by an acute porphyria, mutation analysis of the HMBS gene followed by porphobilinogen deaminase assay is an effective strategy for diagnosis or exclusion of AIP.